The ability of viruses to kill cancer cells is known for more than a century [Kelly, E.; Russell, S. J. History of oncolytic viruses: genesis to genetic engineering. Mol. Ther. 2007, 15, pp. 651-659] and there were numerous promising successes in experimental cancer therapy with various viruses, nevertheless their use in clinical practice is hampered by the difficulty to foresee the interaction between the tumour and its host, as well as the virus and response of human immune system to viral antibodies.
Although the clinical investigations regarding the use of viruses in cancer therapy commenced more than 50 years ago, at present only two viruses are approved for clinical use in cancer therapy. They are adenovirus with deleted E1B 55K gene (Garber, K. China approves world's first oncolytic virus therapy for cancer treatment. J. Natl. Cancer Inst. 2006, 98., pp. 298-300) and unmodified passivized Picomaviridae Enterovirus of Echo type (Eurasian patent 007839; European patent application 03733607), acting as antitumour immunostimulant.
Therefore, the development of novel efficient oncolytic viruses is still a topical problem (Han Hsi Wong, Nicholas R. Lemoine,Yaohe Wang, Viruses 2010, 2, pp. 78-106).
In order to increase the potential of virus so selectively infect cancer cells and heighten the oncolytic activity, a number of modified viruses have been disclosed. They are characterised by deletion of specific genes, thus preventing their propagation in normal cells, or integration of additional genes for improving the oncolytic properties.
However, the limited knowledge concerning the genetical modifications that provide for selectivity and efficiency against the tumour cells, results in modified viruses with lower cytolytic activity, compared to origin, or higher anti-virus response of human immune system (S.Meerani, Yang Yao, Oncolytic viruses in cancer therapy. European Journal of Scientific Research, vol. 40 no. 1 (2010), pp. 156-171; Han Hsi Wong, Nicholas R. Lemoine,Yaohe Wang, Viruses 2010, 2, 78-106).
Although viruses are well-established tools for conveying vectors into cell, their use is limited by the high immunogenicity of viruses (Peng, Z. Current status of gendicine in China: recombinant human Ad-p53 agent for treatment of cancers. Hum. Gene. Ther. 2005, 16, 1016-1027).
One of the most serious adverse properties of non-modified ECHO type viruses, including ECHO 7, is their ability to cause infections that may have a fatal result (Wreghitt T. G., Gandy G. M., King A., Sutehall G., Fatal neonatal ECHO 7 virus infection, The Lancet, vol. 324, p.465, 1984). These viruses are known to be responsible for hand, foot and mouth disease in Malaysia (http://www.vadscomer.com/echovirus7.html), for myocarditis in leukemic child (Midula M., Marzetti G., Borra G., Sabatino G., Myocarditis associated with ECHO 7 type infection in leukemic child, Acta Paediatrica Volume 65, Issue 4, pp. 649-651, July 1976), aseptic meningitis, paralytic disease and fever (http://virology-online.com/viruses/Enteroviruses6.htm). Therefore pathogenicity is one of the major limitations that must be overcome in using ECHO 7 type viruses in treating cancer patients.